Glucans are a heterogeneous group of glucose polymers found in the cell walls of plants, bacteria and fungi. The basic structure of branched glucan consists of a linear backbone of β-1,3-linked glucose with β-1,6-linked side branches of β-1,3-glucan. β-1,3-glucan is the component responsible for the majority of biological activities of zymosan, a commonly used leukocyte stimulant derived from the cell wall of Bakers yeast (Saccharomyces cerevisiae).
Beta-glucans have been tested for tumor therapy in mice for nearly 40 years1,2. Several forms of mushroom-derived beta-glucans are used clinically to treat cancer in Japan, including PSK (from Coriolus versicolor), Lentinan and Schizophyllan. In randomized trials in Japan, PSK has moderately improved survival rates in some cancer trials after gastrectomy3,4, colorectal surgery5,6, and esophagectomy7 to remove primary tumors. Results have been less encouraging in breast cancer8,9 and leukemia10. Schizophyllan also moderately improved survival of patients with operable gastric cancer11, inoperable gastric cancer12,13, and cervical cancer14. While beta-glucans are not widely used by Western oncologists, beta-glucan containing botanical medicines such as Reishi and maitake15 are widely used by U.S. cancer patients as alternative/complementary cancer therapies.
In Europe and USA, beta-glucans especially from Bakers' yeast have long been employed as feed additives for animals, as dietary supplement for humans17, in treatment of wounds18, and as an active ingredient in skin cream formulations. The basic structural unit in beta-glucans is the β(1→3)-linked glucosyl units. Depending upon the source and method of isolation, beta-glucans have various degrees of branching and of linkages in the side chains. The frequency and hinge-structure of side chains determine its immunomodulatory effect. Beta-glucans of fungal and yeast origin are normally insoluble in water, but can be made soluble either by acid hydrolysis or by derivatization introducing charged groups like -phosphate, -sulphate, -amine, -carboxymethyl and so forth to the molecule19-20.
Previous studies that looked for a therapeutic effect of beta-glucan did not incorporate co-administration of therapeutic monoclonal antibodies (MoAb) as part of the protocol. When beta-glucan is administered without co-administration of MoAb, its tumor cytotoxic effect requires the presence of naturally-occurring antitumor antibodies which can be quite variable among patients and even in experimental mice. Thus, it is of interest to determine the therapeutic effects of co-administering beta-glucan and therapeutic monoclonal antibodies. It is also not clear whether therapeutic effect can be obtained by orally administered beta-glucan.